Personalized Antiemetic Regimen According to Patients' Pharmacogenetic Profile

Official title

Randomized Phase II Study of Personalized Antiemetic Regimen Based on Pharmacogenetic Profile for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Chinese Breast Cancer Patients.

Overview

The objectives of this study are to determine if pharmacogenetic (PG) analysis of an individual enable optimal selection of antiemetic regimen for patients undergoing the first cycle of AC (Adriamycin + Cyclophosphamide) or FEC (Fluorouracil + Epirubicin + Cyclophosphamide) chemotherapy. It also aims to compare the quality of life of patients in the first cycle of AC / FEC chemotherapy with and without PG analysis. Patients will be randomized to undergo PG analysis \[PG group\] versus no PG analysis \[Non-/+PG group\]. Those in the PG group would be offered currently available optimal antiemetic prophylaxis, with or without Olanzapine according to PG outcomes. Those in the Non-PG group would be offered currently available optimal antiemetic prophylaxis.

Interventions

• Drug Standard antiemetic regimen or Olanzapine antiemetic regimen
  Standard antiemetic regimen: * Day 1: Aprepitant 125mg QD (once daily); Ondansetron 8mg BD (twice daily); Dexamethasone 12mg QD (Aprepitant, Ondansetron and Dexamethasone to be take 60 minutes before chemotherapy on Day 1) * Days 2 to 3: Aprepitant 80mg QD Olanzapine antiemetic regimen: * Day 1: Aprepitant 125mg QD; Ondansetron 8mg BD; Dexamethasone 12 mg QD; Olanzapine 10mg QD (Aprepitant, Ondansetron and Dexamethasone to be take 60 minutes before chemotherapy on Day 1); Olanzapine 10mg noct
• Drug Standard antiemetic regimen
  * Day 1: Aprepitant 125mg QD; Ondansetron 8mg BD; Dexamethasone 12mg QD (Aprepitant, Ondansetron and Dexamethasone to be take 60 minutes before chemotherapy on Day 1) * Days 2 to 3: Aprepitant 80mg QD

Primary outcome measures

• Complete Protection (CP) [Time frame: 2 years]

Secondary outcome measures (1)

• No Nausea (NN) [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• Chinese patient, female >/=18 and < 75 years of age.
• Patient is diagnosed with early breast cancer.
• Patient is naïve to emetogenic chemotherapy moderately or highly emetogenicity.
• Patient is scheduled to receive her first course of neoadjuvant/adjuvant chemotherapy for breast cancer follows: AC: Intravenous (IV) Adriamycin 60 mg/m\^2 + Cyclophosphamide 600 mg/m\^2, given as 14-day cycle or 21-day cycle, or FEC: IV Fluorouracil 500 mg/m\^2 + Epirubicin 50 mg/m\^2 + Cyclophosphamide 500 mg/m\^2, given as 21-day cycle
• Patient has a predicted life expectancy of 4 months.
• Patient has ECOG (Eastern Cooperative Oncology Group) Performance Status of 0-1.
• Premenopausal female patients must not be pregnant (documented negative urine pregnancy test).
• Patient is able to read, understand and complete study questionnaires and diary, including questions requiring a visual analog scale (VAS) response.
• Patient understands the procedures and agrees to participate in the study by giving written informed consent.

Exclusion criteria

• Patient with advanced breast cancer.
• Patient receiving cisplatin or any other chemotherapy of higher emetogenic potential, except for cyclophosphamide and doxorubicin in the regimens described above.
• Patients who are scheduled to receive concurrent radiation as part of their chemotherapy regimen for their malignancy
• Patients who experience any vomiting or grade 2-3 nausea per Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v 4.03) in the 24 hours before Day 1 of chemotherapy
• Patient has a history of treatment with moderately to highly emetogenic chemotherapy.
• Patient has an active infection (e.g., pneumonia, systemic fungal infection) or any uncontrolled disease (e.g., diabetes mellitus, hypertension) which, in the opinion of the investigator, might confound the results of the study or pose unwarranted risk.
• Patient with history of glaucoma, dementia, seizures, Parkinson's disease, Neuroleptic Malignant Syndrome (NMS), thromboembolic events.
• Patient currently uses any illicit drugs, including marijuana, or has current evidence of alcohol abuse as determined by the investigator.
• Patient is mentally incapacitated or has a significant emotional or psychiatric disorder that, in the opinion of the investigator, precludes study entry.
• Patients who are regular alcohol drinker or smoker
• Patient has a history of any illness that, in the opinion of the investigator, might confound the results of the study or pose unwarranted risk.
• Patient has a history of hypersensitivity to aprepitant, ondansetron or dexamethasone.
• Patients who have phenylketonuria and abnormal uric acid.
• Any investigational drugs taken within 4 weeks prior to Day 1 of cycle 1, and/or is scheduled to receive any investigational drug during the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

Hong Kong · 1 center

• Department of Clinical Oncology, Prince of Wales Hospital — Hong Kong

Identifiers

NCT: NCT07455955 · SYM014

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗